The author proposes to study the induction of metastases from embryonal carcinoma cells conditioned by host-derived growth factors/modulators. Our studies have shown that the 402AX ECC is normally a non-metastatic embryonal carcinoma, which in the presence of host-derived growth factors becomes metastatic. The production of metastases using this model appears to be epigenetic, since the progeny of transplanted metastases fail to metastasize. Host-derived growth factors/modulators are generated from uterine and peritoneal extracts of early pregnant or estrogen-treated mice. Using the above experimental system, a comparative analysis of these nascent soluble factor(s) by adhesive/aggregation, mitogenic and migratory assays, as well as high resolution techniques will be pursued. A series of experiments is proposed to determine what biological activities are associated with partially purified estrogen-induced growth factor(s). These experiments will involve the effects of host-factors on 402AX ECC in vivo and in vitro in order to determine how they affect secondary tumor growth. The final proposal is to determine the tissue distribution of these factors by the development of quantitative assays. The overall objective of this proposal is to determine: 1) the mechanism whereby circulating and dormant tumor cells can be recruited to metastatic status by the exposure to growth factor(s)/modulators, 2) what biochemical and cellular changes accompany the metastatic phenotype, and 3) the tissue distribution of these factors and their role in embryonic implantation and development.